tbuckley/cabot-search huggingface dataset:
Abstract 15614: Pericardial and Abdominal Visceral Adiposity Are Associated With Increased Risk of Hospitalization or Death From SARS-CoV-2 Infection: A Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study
Authors: Asma Sharaf, James G Terry, Pallavi Balte, Jeffrey Carr, Matthew Allison, Cheryl A Anderson, Surya Bhatt, Michelle Long, Michael Shashaty, Nadine Al-Naamani, Jason D Christie, Elizabeth Oelsner, Michaela R Anderson
Journal: Circulation (2023)

Background Obesity increases risk of death from SARS-CoV-2 infection. Excess ectopic fat may increase this risk through inflammation, hypercoagulability, and immune dysfunction. We hypothesized that greater pericardial (PAT) and visceral adipose tissue (VAT) would associate with higher risk of hospitalization or death from SARS-CoV-2. Methods C4R collected SARS-CoV-2 outcomes from US-based cohort studies. These were linked to chest and abdominal CT scans obtained from Jackson Heart (2007-2010) and CARDIA (2010-2011) studies. We standardized PAT across cohorts and VAT within each cohort to account for differences in VAT measurement protocols. Our outcome was COVID-related hospitalization or death from March 2020 to February 2023 assessed via questionnaires, serosurvey, and record review. Logistic regression models were adjusted for age, sex, race/ethnicity, education, smoking status, and cohort. We adjusted for body mass index (BMI) at COVID assessment in secondary models. Results We included 3002 subjects with mean (SD) age of 62 (6) years, of whom 62% were women, 41% White, 59% Black, 59% never smokers, and 13% current smokers. Sixty-one subjects (2%) had SARS-CoV-2 related hospitalization or death. Every 1-standard deviation (SD) increment in PAT volume was associated with 79% higher odds of hospitalization or death (95%CI 1.38-2.33, Fig A); the estimate was similar after adjusting for BMI (OR 1.71, 95%CI 1.27-2.31). Abdominal VAT was associated with higher odds of hospitalization or death (OR 1.47 per 1 SD, 95%CI 1.20-1.81, Fig B), even after adjustment for BMI (OR 1.35, 95%CI 1.05-1.72). Conclusion Greater pericardial or visceral adiposity measured 10-15 years prior to SARS-CoV-2 emergence, was associated with higher odds of hospitalization or death from SARS-CoV-2 independent of BMI. Lowering PAT and VAT may have collateral benefit for those who develop SARS-CoV-2 infection. Further study of the role of visceral adipose in viral infection is needed.
Abstract 13863: Computed Tomography Angiography Characteristics of Thin-Cap Fibroatheroma in Patients With Diabetes Mellitus
Authors: Keishi Suzuki, Daisuke Kinoshita, Takayuki Niida, Haruhito Yuki, Daichi Fujimoto, Damini Dey, Hang Lee, Iris McNulty, Masamichi Takano, Kyoichi M Mizuno, Maros Ferencik, Tsunekazu Kakuta, Ik-kyung Jang
Journal: Circulation (2023)

Background: It was recently reported that thin-cap fibroatheroma (TCFA) detected by optical coherence tomography (OCT) was an independent predictor of future cardiac events in patients with diabetes mellitus. However, OCT requires invasive procedure including intracoronary imaging. Computed tomography angiography (CTA) characteristics of TCFA have not been systematically studied. Aims: The aim of this study was to investigate CTA characteristics of TCFA in patients with diabetes mellitus. Methods: Patients with diabetes mellitus who underwent pre-intervention CTA and OCT were enrolled. Non-culprit lesions with a diameter stenosis of ≥30% on angiogram were assessed. Plaque volume and high-risk plaque (HRP) features were evaluated by CTA. Results: Among 132 plaques in 106 patients with diabetes mellitus, 31 plaques had TCFA. Fibrofatty and necrotic core (FF + NC) volume (-30 to 130 HU) was higher in TCFA than in non-TCFA (125.5 mm 3 vs. 59.4 mm 3 , p &lt;0.001). The prevalence of positive remodeling (90.3% vs. 44.6%, p &lt;0.001), low attenuation plaque (80.6% vs. 28.7%, p &lt;0.001), and napkin-ring sign (77.4% vs. 11.9%, p &lt;0.001) was significantly higher in TCFA than in non-TCFA. The difference in the prevalence of spotty calcification between TCFA and non-TCFA was not statistically significant (19.4% vs. 15.8%, p = 0.608). In multivariable logistic regression analysis, FF + NC volume ≥103.7 mm 3 (OR: 6.8; P &lt;0.001) and HRP features ≥2 (OR: 11.7; P &lt;0.001) were associated with TCFA. The addition of FF + NC volume ≥103.7 mm 3 to HRP features ≥2 significantly increased the area under the curve for detection of TCFA (AUC = 0.766 [95% CI; 0.673-0.859] vs AUC = 0.820 [95% CI; 0.736-0.904]; p = 0.012). Conclusions: FF + NC volume and HRP features on CTA were associated with OCT-detected TCFA. CTA may be helpful in identifying high-risk plaques in patients with diabetes mellitus.
Abstract 12593: Associations of Serum Uric Acid and Cardiovascular Events in a Clinical Trial of IL-1β Blockade
Authors: Nicholas H Adamstein, Jean MacFadyen, Brittany N Weber, Peter Libby, Daniel Solomon, Paul M Ridker
Journal: Circulation (2023)

Background: Serum uric acid (SUA) associates with CV events, mortality, and gout. We assessed whether SUA predicts CV risk in a trial of IL-1β inhibition with canakinumab, a therapy known to reduce both CV events and gout. Aims: To validate associations between SUA and CV risk in a large cohort with chronic CAD and determine whether these associations were altered by IL-1β blockade or baseline renal function. Methods: The Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) randomized 10,061 patients with prior MI and hsCRP ≥ 2 mg/L to canakinumab 50 mg, 150 mg, 300 mg, or placebo subcutaneously every four weeks. SUA levels were obtained at baseline. Cox proportional hazards models compared the outcomes of major adverse cardiovascular events (MACE), CV death (CVD), and all-cause mortality (ACM) among those with baseline SUA ≤ 6.8 mg/dL, 6.8- 9.0 mg/dL, and ≥ 9.0 mg/dL (format: HR (95% CI); p). This analysis was repeated separately within canakinumab, placebo, eGFR ≥ 60 mL/min, and eGFR &lt; 60 mL/min sub-groups. Results: High SUA associated with MACE (1.66 (1.38-1.99); p&lt;0.0001), CVD (2.52 (1.98-3.21); p&lt;0.0001), and ACM (2.43 (2.01-2.94); p&lt;0.0001) compared to low SUA. These associations were minimally attenuated after adjustment for age, sex, BMI, smoking, hypertension, diabetes, LDL-C, and hsCRP. After further adjusting for eGFR and diuretic use, high SUA independently predicted CVD and ACM. In the IL-1β blockade arm, high SUA associated with MACE (1.82 (1.46-2.26); p&lt;0.0001), CVD (2.80 (2.10-3.73); p&lt;0.0001), and ACM (2.72 (2.17-3.40); p&lt;0.0001). In participants with normal eGFR, high SUA associated with CVD and ACM, but not MACE. Conclusions: These data from a large cohort of patients with chronic CAD confirm that individuals with elevated SUA have increased CV risk despite aggressive medical therapies. IL-1β blockade did not modify these associations. Future trials may consider inclusion of patients with high SUA and CKD as a method to increase absolute risk.
Abstract 16949: The Effects of the Technology-Based Family-Centered Empowerment (T-FamE) Heart Failure Transitional Program: Preliminary Analysis of a Randomized Controlled Trial
Authors: Doris S yu, Polly Wai Chi W Li, Chi Wing Wong, Victor Cheng
Journal: Circulation (2023)

Introduction: Health digitization and advanced dyadic science offer new opportunities to enhance the transitional care model for heart failure (HF). The T-FamE program a transitional care model integrating digital health and optimized carer support to enhance the post-discharge outcomes of HF patients. Hypothesis: The T-FamE was more effective than usual care to enhance self-care, perceived control, family function, HRQoL and hospital readmission of HF patients. Methods: From Aug 2021 to March 2022, a RCT randomized 170 post-discharge HF patients (mean age = 69.0; SD=11.5; NYHA Grade II/III/IV = 53.9/40.6/.5.5%. LVEF&lt;40% =58.5%) to the T-FamE or usual care. The 12-week nurse-delivered T-FamE comprises an interactive mobile Apps, which allows i) proactive health monitoring with tailored autonomous guideline-based feedback; ii) family-centerd goal-setting on self-care, iii) personalized drug education, iv) mobile access to nurse, v) video-based HF compass for rehabilitation and self-care. The cardiac nurse conducted three monthly visits for family-based empowerment on disease management. Outcome evaluation by Self-care Heart Failure index, Self-care Self-Efficacy Scale, Control Attitude Scale, Family Functioning Device and EuroQoL at baseline and post-test. Results: Two-way analysis of covariance showed significant greater improvement of T-FamE group on self-care maintenance (F=21.46, p&lt;0.001, η 2 p =0.113), management (F=22.52, p=0.01, η 2 p =0.118), symptom perception (F=69.70, p&lt;0.001, η 2 p =0.29) and confidence (F=13.36, p&lt;0.001, η 2 p =0.073) than the control. They have greater improvement in EuroQoL (F=5.78, p=0.017, η 2 p =0.033) and sense of control (F=5.78, p=0.017, η 2 p =0.033), and significantly lower number ore readmission in one year (-0.278 (95%CI=-0.54, -0.008, p=0.043). Conclusions: The T-FamE is effective to improve the self-care, HRQL and readmission outcomes. Digitalized transitional care model with optimized family support play explain the therapeutic benefits. Autonomous response to health monitoring data may enhance self-care decision-making.
Abstract 15609: ParSE-seq: A Calibrated Multiplexed Assay for Clinical Interpretation of Putative Splice-Altering Variants
Authors: Matthew J Oneill, Tao Yang, Julie Laudeman, Maria Calandranis, Andrew Glazer, Dan M Roden
Journal: Circulation (2023)

Background: Up to 10% of disease-associated variants are predicted to affect RNA-splicing. Interpreting the clinical significance of putative splice-altering variants outside the 2-base pair canonical splice sites remains difficult without functional studies. Goal: To develop a calibrated, high-throughput assay to adjudicate variant effects on RNA splicing. Methods: We established Parallel Splice Effect Sequencing (ParSE-seq), a multiplexed minigene assay, to test variant effects on RNA splicing quantified by high-throughput sequencing. We used the tool SpliceAI to prioritize exonic and intronic candidate splice variants, and ClinVar to select curated benign and pathogenic controls in SCN5A , which encodes the major voltage-gated cardiac sodium channel. We transfected 271 barcoded minigene constructs into HEK cells or induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), and calibrated to the American College of Medical Genetics and Genomics scheme. Variants were interpreted using the calibrated functional data, and experimental data correlated to SpliceAI predictions. We studied selected variants by automated patch clamp (APC) in HEK cells and by assessing splicing and channel function directly in CRISPR-edited iPSC-CMs. Results: ParSE-seq revealed the splicing effect of 245 SCN5A variants in iPSC-CMs. The assay had concordant scores for 43/45 benign and pathogenic control variants, achieving both PS3- and BS3-strong levels of evidence after calibration. 41/114 exonic variants and 30/66 intronic variants with determinate scores disrupted splicing. 9 of 42 Variants of Uncertain Significance were reclassified, and 30 of 34 variants with conflicting interpretations were reinterpreted using the functional data. Predictions from SpliceAI performed well on experimental data (AUC = 0.96). We identified 3 clinically relevant splice-altering missense variants that had normal function when tested with a cDNA-based APC assay. A splice-altering intronic variant, c.1891-5C&gt;G also disrupted splicing and sodium channel electrophysiology when introduced into iPSC-CMs by CRISPR-editing. Conclusions: ParSE-seq is an efficient, calibrated, high-throughput assay to facilitate splice-altering variant interpretation.
Transcriptional regulation of amino acid metabolism by KDM2B, in the context of ncPRC1.1 and in concert with MYC and ATF4
Authors: Evangelia Chavdoula, Vollter Anastas, Alessandro La Ferlita, Julian Aldana, Giuseppe Carota, Mariarita Spampinato, Burak Soysal, Ilaria Cosentini, Sameer Parashar, Anuvrat Sircar, Giovanni Nigita, Lalit Sehgal, Michael A Freitas, Philip N Tsichlis
Journal: Metabolism (2023)
Abstract 13832: XplainScar: Explainable Artificial Intelligence to Identify and Localize Left Ventricular Scar in Hypertrophic Cardiomyopathy (HCM) Using 12-lead Electrocardiogram
Authors: Kasra Nezamabadi, Sanjay Sivalokanathan, Jiwon Lee, Meiling Chen, Daiyin Lu, Parvin Mousavi, M Roselle Abraham
Journal: Circulation (2023)

Background/Rationale: Myocardial scar, identified by late gadolinium enhancement (LGE) on MRI, is associated with sudden death in HCM. Unlike ECG, MRI is expensive and adversely affected by artifacts from implanted devices. However, little is known about ECG features of LV-scar in HCM. Objective: Develop an ECG-based explainable machine learning method to identify and localize LV-scar in HCM. Method: We retrospectively studied 500 HCM patients (JH HCM Registry) for model development, and 248 patients (UCSF HCM Registry) for validation. All patients underwent MRI and ECHO within 1 year of ECG. LV-LGE (scar) was assessed using QMass. After excluding RV-insertion-point-LGE, the LV was divided into basal, mid, and apical regions for scar detection. Resting 12-lead ECGs were segmented, features were extracted and adjusted for LV-mass, age, sex. We utilized unsupervised and self-supervised ECG representation learning, where patients are partitioned into groups of several sub-clusters, each sharing similar ECG patterns, but with high separation between scar and no-scar classes. In each group, a self-supervised neural net and a fully connected neural net successfully predicted LV-scar (see Figure) and revealed ECG features of scar. Results: Our method identifies LV-scar in the JH-dataset with high precision (90%), sensitivity (95%), specificity (80%), F1-score (90%), and generalizes well to UCSF-data (precision:88%, sensitivity:90%, specificity:78%, F1-score:89%). The top ECG features for basal-scar are Q-amplitude, Q-slope, non-terminal QRS duration in aVR, and area under QRS and T wave energy in V1-V2. T-wave inversion in V4-V6, area under QRS in V3, TP slope in V3-V4 predicted apical scar. Features selected for mid scar prediction combine features for basal and apical scar. Conclusion: This is the first ECG-based ML model to identify/localize LV-scar in HCM. Our model demonstrates good performance and reveals ECG features of scar in HCM.
Abstract 13828: Aptamer Proteomics for Biomarker Discovery in Heart Failure With Preserved Ejection Fraction: The PARADIGM-HF Proteomic Sub-Study
Authors: Natasha Patel-Murray, Luqing Zhang, Brian Claggett, Dongchu Xu, Pablo Serrano-Fernandez, Simon Wandel, Huilei Xu, Margaret Healey, Gordon Turner, Chien-Wei Chen, Faye Zhao, WILLIAM A CHUTKOW, Denise Yates, Christopher ODonnell, Margaret Prescott, Martin P Lefkowitz, Claudio R Gimpelewicz, Michael Beste, Liangke Gou, Akshay S Desai, Pardeep S Jhund, Milton Packer, Marc A Pfeffer, Margaret M Redfield, Jean L Rouleau, Faiez ZANNAD, Michael R Zile, John J McMurray, Michael Mendelson, Scott D Solomon, Jonathan Cunningham
Journal: Circulation (2023)

Introduction: Prognostic markers and biological pathways linked to detrimental clinical outcomes in heart failure with preserved ejection fraction (HFpEF) remain incompletely defined. Goal: To identify serum proteins associated with risk for HF hospitalization (HFH) and cardiovascular (CV) death in patients with HFpEF, including proteins with differential associations with clinical outcomes in HFpEF compared to HFrEF. Methods: We measured serum levels of 4123 unique proteins in 1117 patients with HFpEF in the PARAGON-HF trial using a modified aptamer proteomic assay. Baseline protein concentrations significantly associated with total HFH and CV death were identified by recurrent events regression, accounting for multiple testing, adjusted for age, sex, treatment, and anticoagulant use, and compared to 2515 patients with HFrEF from the PARADIGM-HF and ATMOSPHERE trials. Results: We identified 288 proteins to be robustly associated with the risk of HFH and CV death (335 events over an average of 2.7 years of follow-up) in a HFpEF trial population. Proteins most strongly related to HFpEF outcomes included B2M, TIMP1, SERPINA4, and SVEP1 ( Figure ). Protein-outcome associations in patients with HFpEF did not markedly differ compared to HFrEF. Just 3 proteins (APOE, RTF1, and VWF) were differentially associated with outcomes between the HF subtypes (FDR &lt;0.05). A proteomic risk score derived in HFpEF patients was not superior to a previous proteomic score derived in HFrEF nor to clinical risk factors, NT-proBNP, or high-sensitivity cardiac troponin. Conclusions: Numerous serum proteins linked to metabolic, coagulation, and extracellular matrix regulatory pathways were associated with worse HFpEF prognosis. SVEP1, a cell adhesion protein recently identified as a HFrEF prognosis biomarker, also strongly predicted risk in HFpEF. Our results demonstrate substantial similarities in serum proteomic risk markers across the EF spectrum.
Abstract 15629: Innovative Approach to Mitral Regurgitation in a Patient With Partially Dehisced Annuloplasty Band After Mitral Valve Repair
Authors: Francisco Borges Alexandrino, Kathleen Kopecky, Arman Arghami, Sorin Pislaru, Lawrence J Sinak, Mohamad Alkhouli, Jared G Bird
Journal: Circulation (2023)

Case: A 65-year-old patient presented 4 months after mitral valve repair (annuloplasty band, commissuroplasty, neo-chordae to the anterior mitral leaflet (AL)). At follow up, he developed significant hemolytic anemia (Hemoglobin 10.1g/dL, LDH 650U/L, Bilirubin 1.4mg/dL and haptoglobin&lt;14 mg/dL). TEE revealed the substrate for hemolysis: moderate-severe mitral regurgitation (MR) starting at the coaptation of A2 and P2 scallops due to AL overriding the posterior (PL). The jet was then directed posteriorly to a small (3 x 6 mm confirmed by cardiac CT) area of annuloplasty band dehiscence at the base of the P2 scallop, with the band in direct path of the flow. The unique feature was that AL retained coaptation with the annuloplasty band, thus forming a small tunnel from the A2-P2 coaptation defect to the dehisced area. Given that redo surgery early after initial intervention would be challenging, the Heart Team decided to pursue percutaneous closure at the level of the dehisced annuloplasty to reduce regurgitation and mitigate hemolysis. Under 3D TEE guidance closure with a 12mm AVP plug was attempted but resulted in interference with PL motion with a new jet of regurgitation laterally. Using two 8mm AVP plugs was successful in closing the dehiscence with minimal impact on PL. Overall regurgitation was reduced to mild. Within a week hemolysis labs improved: LDH337 U/L, Bilirubin0.7 mg/dL. Discussion: Annuloplasty band dehiscence is a known cause of recurrent MR after repair. As regurgitation occurs at the leaflet coaptation zone, percutaneous closure of these defects is usually futile. In this patient we took advantage of the maintained coaptation between the AL and annuloplasty band.
Abstract 13815: Therapeutic Effects of Empagliflozin in Diabetic Patients After Acute Myocardial Infarction: Systematic Review and Meta-Analysis With Trial Sequential Analysis
Authors: Adel Mouffokes, Youssef Soliman, Basma E Amer, Tungki Pratama Umar, Basel Abdelazeem
Journal: Circulation (2023)

Introduction: Empagliflozin is a new sodium-glucose transporter protein 2 (SGLT2) inhibitor. In addition to its anti-hyperglycemic effect, recent studies suggested that it may improve cardiac outcomes in diabetic patients with acute myocardial infarction. This systematic review and meta-analysis aims to test this hypothesis. Methods: We comprehensively searched PubMed, Scopus, Cochrane, and Web of Science. We included studies comparing empagliflozin versus placebo in diabetic patients with acute myocardial infarction. Our outcomes were the changes in plasma N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), left ventricular ejection fraction% (LVEF%), and hemoglobin A1c (HbA1c) levels. We performed Trial Sequential Analysis (TSA), and we used mean difference (MD) and 95% confidence interval (CI) as our effect size with a random effects model. Results: Five studies (one cohort study and four randomized controlled trials), compromising 751 patients, were included. Empagliflozin significantly increased LVEF compared to placebo (MD = 1.80, 95% CI [0.50, 3.10], P =0.007), however, the TSA curve did not cross the conventional boundary for statistical significance, indicating that the available evidence did not reach the predetermined threshold. On the other hand, we observed no significant difference between the two groups in terms of NT-pro-BNP and HbA1c (MD = -136.59, 95% CI [-293.43, 20.25], P =0.09; MD= -0.72, 95% CI [-1.73, 0.29], P =0.16, respectively). Conclusions: Our meta-analysis reveals that among diabetic patients with acute myocardial infarction, empagliflozin failed to improve cardiac parameters such as LVEF and NT-pro-BNP without providing additional benefits in reducing HbA1c levels. Therefore further large-scale RCTs are warranted to ascertain our findings.
Abstract 12517: The Racial Disparity Among the Clinical Outcomes, and Management Utilization in Atrial Fibrillation Patients: A Meta Analysis
Authors: Vikash Jaiswal, Akash Jaiswal, Novonil Deb, Abdelrahman Attia, Song Peng Ang, Endurance O Evbayekha, Shiva Gupta, Dharshana Prem Anand, Nirmit Patel
Journal: Circulation (2023)

Background: Although a higher burden of atrial fibrillation (AF) risk factors exists among the Black population, their prevalence of AF is less than White patients due to the under-diagnosis of minority groups and disparities in their management and outcomes. Objective: We aim to evaluate the disparities among the clinical outcomes post-AF, utilization of oral anticoagulants, and catheter ablation among Black and White race of patients. Methods: We systematically searched all electronic databases from inception until 27th May 2023. The primary outcome was all-cause mortality (ACM). Secondary outcomes include incidence of stroke, utilization of direct oral anticoagulants (DOAC), and catheter ablation. Results: A total of 11 studies with 1915540 patients were included in the final analysis (1771768 patients in the White group and 143772 patients of Black race). Pooled analysis of clinical outcomes shows that Black patients were having a higher risk of all-cause mortality (HR, 1.39(95%CI:1.09-1.75), P&lt;0.01). Similarly compared with White patients, the odds of initiating DOAC therapy (OR, 0.85(95%CI: 0.80-0.91), P&lt;0.001), and utilization of catheter ablation (OR, 0.69(95%CI: 0.52-0.86), P&lt;0.001) were significantly lower in Black patients. Conclusion: Black patients with atrial fibrillation are found to be associated with higher mortality and lower utilization of management approaches like use of DOAC, and catheter ablation.